Cyclic cis-1-amino-2-alkanols are useful as chiral auxiliaries and as intermediates in the synthesis of pharmaceuticals. For example, optically pure cis-(1S,2R)-1-amino-2-indanol(I) ##STR1## has been used as an intermediate in the preparation of HIV-1 protease inhibitors for anti-viral and anti-AIDS therapy (T. J. Tucker et al. J. Med. Chem. 35, 2525-2533 (1992); S. D. Young et al. J. Med. Chem. 35, 1702-1709 (1992); W. J. Thompson et al. J. Med. Chem. 35, 1685-1702 (1992)). In addition, optically pure cis-1-amino-2-indanol has been used as a chiral auxiliary for the asymmetric addition of amide homoenolates to aldehydes (J. D. Armstrong, III, et al. Tetrahedron Lett. 44, 6599-6602 (1992)).
Cyclic cis-1-amino-2-alkanols are commonly prepared from the corresponding trans-1-amino-alkanols, which are synthetically much more accessible. For example, Lutz and Wayland have described the preparation of racemic cis-1-amino-2-indanol from racemic trans-1-amino-2-indanol in three steps (R. E. Lutz and R. L. Wayland, Jr., J. Am. Chem. Soc. 73, 1639-1641 (1951)). Their synthesis is a particular application of what appears to be the most popular method for converting trans aminoalcohols to cis aminoalcohols. It involves the synthesis of an oxazoline by the treatment of the amide with thionyl chloride. The oxazoline is isolated, usually by crystallization for the purpose of purification, and subsequently hydrolyzed, theoretically via an ester-ammonium salt, to the cis aminoalcohol.
Optically pure cis-(1S,2R)-1-amino-2-indanol has also been obtained by the resolution of the corresponding L-phenylalanine amide diastereomers by chromatographic separation, followed by cleavage of the amide with sodium in ethanol (W. J. Thompson et al. J. Med. Chem. 35, 1685-1701 (1992)).
These and other known processes for the preparation of cyclic cis-1-amino-2-alkanols often involve lengthy synthetic transformations and usually provide the desired product in low overall yield. Resolution procedures for obtaining optically pure cis-(1S,2R)-1-amino-2-indanol are notoriously inefficient. A practical preparation of cyclic cis-1-amino-2-alkanols, particularly of optically pure cis-1-amino-2-indanol, would be highly desirable.
It is, therefore, an object of the present invention to provide a process for the preparation of cyclic cis-1-amino-2-alkanols from the corresponding cyclic trans-1-amino-2-alkanols or their amides. It is a particular object of the present invention to prepare cis-1-amino-2-indanol from trans-1-amino-2-indanol in good yield and with a minimum of synthetic manipulations. It is also an object of the present invention to prepare optically pure cis-1-amino-2-alkanols such as cis-(1S,2R)-1-amino-indanol, from the corresponding partially resolved or optically pure trans-1-amino-2-alkanols in good yield and with minimum synthetic transformations.